Penam → (2R,3S,5R,6R) 2-(N-acetyl)carbamoyloxymethyl-2-methyl-6-phenoxyacetamidopenam-3-carboxylic acid p-nitrobenzyl ester

HRID 463365Notes

Reaction equation

HRID 463365 reaction equation
[N+:1]([C:4]1[CH:35]=[CH:34][C:7]([CH2:8][O:9][C:10]([C@@H:12]2[N:16]3[C:17](=[O:30])[C@@H:18]([NH:19][C:20](=[O:29])[CH2:21][O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[C@H:15]3[S@@:14](=O)[C:13]2([CH3:33])[CH3:32])=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2].[C:36]([N:39]=[C:40]=[O:41])(=[O:38])[CH3:37].S1[C@@H]2CC(=[O:49])N2CC1>O1CCOCC1>[N+:1]([C:4]1[CH:35]=[CH:34][C:7]([CH2:8][O:9][C:10]([C@@H:12]2[N:16]3[C:17](=[O:30])[C@@H:18]([NH:19][C:20](=[O:29])[CH2:21][O:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[C@H:15]3[S:14][C@:13]2([CH2:33][O:41][C:40](=[O:49])[NH:39][C:36](=[O:38])[CH3:37])[CH3:32])=[O:11])=[CH:6][CH:5]=1)([O-:3])=[O:2]

Participants

5

Reactant 3

HCID 9548842PenamHCID 11145535(1S,3S,5R,6R) 2,2-dimethyl-6-phenoxyacetamidopenam-3-carboxylic acid-1-oxide p-nitrobenzyl esterHCID 12300404Acetyl isocyanate

Product 1

HCID 12817532(2R,3S,5R,6R) 2-(N-acetyl)carbamoyloxymethyl-2-methyl-6-phenoxyacetamidopenam-3-carboxylic acid p-nitrobenzyl esterYield 40.2%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A solution of (1S,3S,5R,6R) 2,2-dimethyl-6-phenoxyacetamidopenam-3-carboxylic acid-1-oxide p-nitrobenzyl ester (25.18 g, 50.0 mmol), acetyl isocyanate (8.50 ml, 9.53 g, 112 mmol), and dioxane (250 ml) was refluxed under nitrogen for 5 hours, cooled and concentrated in vacuo to a yellow foam. The foam was chromatographed on silica gel (1.7 Kg) with methylene chloride:acetone; 9:1; v:v to give four products; the 3-methyl-Δ3 -cephem; starting sulfoxide, the title penam, and the cephem (in order of elution). The penam fractions were concentrated to a colorless foam in 40.2% yield (11.80 g). Re-chromatography of a portion gave an analytical sample: m.p. 83°-85°; nmr 100 MHz (CDCl3) ppm 8.40 (1,s, ##STR59## 8.20 (2, d, J=8.5, 1/2 aromatic AB pNB), 7.56 (3, d, J=8.5 over m, 1/2 AB, pNB and C6 --NH), 7.5 (2, m) and 6.9 (3, m, O--Ph--H's), 5.7 (2, m's, C5 --C6 --H's), 5.32 (2, br s, pNB methylene), 4.88 (1, s, C3 --H), 4.56 (2, s, ##STR60## 4.26 and 4.06 (2, d's,J=11.5, AB of C2 --CH2O), 2.22 (3, s, ##STR61## and 1.47 (3, s, C2 --CH3); nmr 13C 4 carbonyls ca 170 ppm, carbamate carbonyl C 157.0, C2 singlet at 67.4, while C2 --CH2O is t at 72.3, and C2 --CH3 is q at 21.7.

Workup

  1. temperaturecooled
  2. concentrationconcentrated in vacuo to a yellow foam
  3. customThe foam was chromatographed on silica gel (1.7 Kg) with methylene chloride
  4. customv:v to give four products
  5. concentrationThe penam fractions were concentrated to a colorless foam in 40.2% yield (11.80 g)
  6. customRe-chromatography of a portion gave an analytical sample

Sources & evidence

ORD record
ord-6b8319b7638b4a5d8fc19c4aa342417e
Source dataset
uspto-grants-1985_05
Patent number
US04518773

Reaction notes

Loading…